This proposal requests support for a Keystone Symposia meeting entitled B Cells: New Insights into Normal versus Dysregulated Function, organized by David J. Rawlings, Frances E. Lund, Stuart G. Tangye and John G. Monroe, which will be held in Whistler, British Columbia, Canada from April 12 - 17, 2011. B lymphocytes play crucial roles in host defense against infection via a series of highly coordinated processes that include cell homing, antigen recognition, antibody secretion, antigen presentation, and cytokine release. To accomplish these myriad functions, B cells must maneuver through a complex series of primary and secondary developmental, homoeostatic, and activation-triggered checkpoints. These checkpoints dictate stochastic and molecularly directed events dependent upon local micro-environments, cell-cell interactions, and interactions with pathogenic or non-pathogenic organisms. Early events in this developmental cascade promote the generation of a diverse B cell antigen receptor repertoire that is essential for both survival and entry into downstream effector populations. In parallel, this repertoire is tested for self-reactivity at multiple steps leading to either loss or expansion of specific clones. Dysregulation of these complex processes can lead, alternatively, to immunodeficiency, autoimmunity, or malignant disease. The overall goal of the 2011 Keystone Symposia meeting on B Cells is to highlight recent studies of normal versus abnormal B cell development and function with an emphasis, whenever possible, to data from studies of humans. PUBLIC HEALTH RELEVANCE: B lymphocytes, or B cells, play a critical role in controlling bacterial, viral, and parasitic pathogens via orchestration of both innate and adaptive immune responses. Dysregulated B cell function can lead to immunodeficiency, autoimmunity, or malignant disease. The Keystone Symposia meeting on B Cells will gather investigators from multiple disciplines involved in studying B lymphocyte biology to share data, discuss research challenges, and collaborate in order to provide insight into how to utilize this information for therapeutic benefit in multiple important human disorders.